X-10109916-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015691.5(WWC3):c.1242G>A(p.Gln414=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00042 in 1,208,748 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 279 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.00044 (0 hom. 273 hem.)
• Consequence: WWC3 NM_015691.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.58

Genes affected

WWC3 (HGNC:29237): (WWC family member 3) This gene encodes a member of the WWC family of proteins, which also includes the WWC1 (KIBRA) gene product and the WWC2 gene product. The protein encoded by this gene includes a C2 domain, which is known to mediate homodimerization in the related WWC1 gene product. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant X-10109916-G-A is Benign according to our data. Variant chrX-10109916-G-A is described in ClinVar as [Benign]. Clinvar id is 729354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC3	NM_015691.5	c.1242G>A	p.Gln414=	synonymous_variant	10/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC3	ENST00000380861.10	c.1242G>A	p.Gln414=	synonymous_variant	10/24	1		P1

Frequencies

GnomAD3 genomes AF: 0.000207 AC: 23 AN: 111332 Hom.: 0 Cov.: 23 AF XY: 0.000179 AC XY: 6 AN XY: 33550

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000947

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00784

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000664

GnomAD3 exomes AF: 0.00103 AC: 185 AN: 180183 Hom.: 0 AF XY: 0.00154 AC XY: 103 AN XY: 66693

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00963

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000445

GnomAD4 exome AF: 0.000443 AC: 486 AN: 1097362 Hom.: 0 Cov.: 31 AF XY: 0.000752 AC XY: 273 AN XY: 363202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00822

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000594

Gnomad4 OTH exome AF: 0.000738

GnomAD4 genome AF: 0.000198 AC: 22 AN: 111386 Hom.: 0 Cov.: 23 AF XY: 0.000178 AC XY: 6 AN XY: 33614

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000946

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00749

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000655

Bravo AF: 0.0000793

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	2.2
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs532504268; hg19: chrX-10077956;